The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.

Rising incidence of heart failure (HF) in the Western world despite advanced clinical care necessitate exploration of further preventive tools and strategies. Lipoprotein(a) [Lp(a)], recognized as one of the major cardiovascular risk factors has also been implicated as a risk factor for HF. However, existing evidence remains inconclusive and that has led us to perform this meta-analysis. PubMed/Medline, EMBASE and Scopus were systematically searched for studies evaluating an association of Lp(a) with occurrence of HF from inception-till November 2023. Random effects models and I² statistics were used for pooled odds ratio (OR) and heterogeneity assessment. We performed leave one out sensitivity analyses by sequentially removing one study at a time and recalculating the pooled effect size. Our search rendered in total 360 studies and after final screening this resulted in 7 Mendelian randomization (MR) design. According to the MR analysis, increasing Lp(a) level were significantly associated with increased risk of HF (OR 1.064, 95 % CI: 1.043-1.086, I²= 97.59 %, P < 0.001). In addition, Leave-one-out sensitivity analysis showed that the effect size did not change substantially by removal of any particular study in MR studies and ORs ranged from 1.051 (when excluding Levin) to a maximum of 1.111 (when excluding Wang or Jiang), hereby confirming the association. We were able to show that by meta-analysis of MR data, increasing lipoprotein (a) levels are associated with an increased risk of HF. Whether this is due to a direct effect on heart muscle contraction or whether this is due to an increased risk of ischemic cardiac disease remains to be elucidated.

Lipoprotein (a) (Lp[a]) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, data on association of Lp(a) with risk of atrial fibrillation (AF) is still limited. We searched PubMed/Medline, Scopus, and EMBASE for studies evaluating the association of Lp(a) with the occurrence of AF until July 2023. Random effects models and I² statistics were used for pooled odds ratios (OR), and heterogeneity assessments. A subgroup analysis was performed based on the cohort population, and a one-out sensitivity analysis was performed. This meta-analysis comprised 275,647 AF cases and 2,100,172 Lp(a) participants. An increase in Lp(a) was associated with an increased risk of AF in mendelian randomization (MR) studies (OR 1.024, 95% CI: 1.007-1.042, I² = 87.72%, P < 0.001). Leave-one-out sensitivity analysis confirmed equivalent results in MR studies. Subgroup analysis of MR studies revealed a higher risk of AF in the European cohort (OR 1.023, 95% CI: 1.007-1.040, I² = 89.05%, P < 0.001) and a low risk (OR 0.940, 95% CI: 0.893-0.990) in the Chinese population. Meta-analysis of the MR data suggested higher levels of Lp(a) were associated with increased risk of AF. Future robust prospective studies are warranted to validate these findings.

Age and sex based coronary artery calcium score (CAC) percentiles have been used to improve coronary artery disease (CAD) risk prediction. However, the main limitation of the CACs percentiles currently in use is that they are often based on single studies. We performed a pooled analysis of all available studies that reported on CAC percentiles, in order to develop more generalizable age and sex nomograms. PubMed/Medline and Embase were searched for studies that reported nomograms of age and sex-based CACs percentiles. Studies were included if they reported data collected among asymptomatic individuals without a history of cardiovascular disease. Absolute CACs for each specific percentile stratum were pooled and new percentiles were generated taking into account the sample size of the study. We found 831 studies, of which 12 met the inclusion criteria. Data on CACs percentiles of 134,336 Western and 33,488 Asians were pooled separately, rendering a weighted CACs percentile nomogram available at https://www.calciumscorecalculator.com. Our weighted percentiles differed by up to 24% from the nomograms in use today. Our pooled age and sex based CACs percentiles based on over 155,000 individuals should provide a measure of risk that is more applicable to a wider population than the ones currently in use and hopefully will lead to better risk assessment and treatment decisions.

RAASi (renin-angiotensin-aldosterone system inhibitors) are suggested as possible treatment option in the early phase of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. A meta-analysis investigating the possible detrimental effects of RAASi on the severity of (SARS-CoV-2) infection showed that ambulatory use of RAASi, by hospitalized patients, has a neutral effect. It is, however, conceivable that this observation is biased by the fact that antihypertensive medications, are often discontinued at or during admission in hospitalized patients with SARS-CoV-2. We, therefore, investigated the effect of discontinuation of antihypertensive medications, in hospitalized patients with SARS-CoV-2. We performed a retrospective observational study on 1584 hospitalized patients with SARS-CoV-2 from 10 participating hospitals in the Netherlands. Differences in the outcome (severity of disease or death) between the groups in which medications were either continued or discontinued during the course of hospitalization were assessed using logistic regression models. Discontinuation of angiotensin receptor blockers, ACE (angiotensin-converting enzyme) inhibitors and β-blockers, even when corrected for sex, age, and severity of symptoms during admission, resulted in a 2 to 4× higher risk of dying from SARS-CoV-2 infection (odds ratio [95% CI]); angiotensin receptor blockers 2.65 [1.17–6.04], ACE inhibitor (2.28 [1.15–4.54]), and β-blocker (3.60 [1.10–10.27]). In conclusion, discontinuation of at-home ACE inhibitor, angiotensin receptor blockers, or β-blocker in patients hospitalized for a SARS-CoV-2 infection was associated with an increased risk of dying, whereas discontinuation of calcium channel blockers and diuretics was not.

Background: Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR‐19b‐1‐5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio‐cerebrovascular (MACCE) events in patients with ACS. Methods and Results: In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR‐19b‐1‐5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow‐up time of 1.01±0.43 years. Low miR‐19b‐1‐5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (‐Log‐miR‐19b‐1‐5p, [unstandardized beta, 44.50; 95% CI, 2.20–86.80; P <0.05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR‐19b‐1‐5p expression was independently associated with a higher risk of MACCE (‐Log‐miR‐19b‐1‐5p, [hazard ratio, 1.85; 95% CI, 1.23–2.80; P <0.05]). Furthermore, a significant interaction was noted between the inverse miR‐19b‐1‐5p expression and family history of premature coronary artery disease ( P =0.01) on the risk of MACCE. Conclusions: Lower miR‐19b‐1‐5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR‐19b‐1‐5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.